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Early lymphocyte expansion is severely impaired in interleukin 7 receptor-deficient mice

Journal of Experimental Medicine (JEM)

December 1994
180(5):1955-60

DOI:10.1084/jem.180.5.1955

Source
PubMed

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CC BY-NC-SA 4.0

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Interleukin 7 (IL-7) stimulates the proliferation of B cell progenitors, thymocytes, and mature T cells through an interaction with a high affinity receptor (IL-7R) belonging to the hematopoietin receptor superfamily. We have further addressed the role of IL-7 and its receptor during B and T cell development by generating mice genetically deficient in IL-7R. Mutant mice display a profound reduction in thymic and peripheral lymphoid cellularity. Analyses of lymphoid progenitor populations in IL-7R-deficient mice define precisely those developmental stages affected by the mutation and reveal a critical role for IL-7R during early lymphoid development. Significantly, these studies indicate that the phase of thymocyte expansion occurring before the onset of T cell receptor gene rearrangement is critically dependent upon, and mediated by the high affinity receptor for IL-7.

. Analysis of High Affinity IL.7 Binding to Control and IL-TR -/-Cells Control IL-7R-/ -

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Targeted disruption of the IL-7R locus and molecular characterization of IL-7K-/-mice. (A) The first six exons encoding the extracellular domain of murine IL-7R are depicted, highlighting the initiation codon (ATG), NH2 terminus (NH2), transmembrane domain (TM), and diagnostic BgllI sites. The vector constructed to target the IL-7R gene and the probe used to identify an IL-7R locus altered by homologous recombination are also shown. (B) DNAs isolated from wild-type mice (+/+), and mice heterozygous (+/-) or homozygous (-/-) for the mutant IL7R gene were digested with BgllI and subject to Southern blot analysis using the indicated probe. The positions of various HindllI X size markers are shown. (C) Reverse transcriptase PCR analysis of splenic cDNA prepared from adult mice heterozygous (+/-) and homozygous (-/-) for the IL-7R mutation using a primer 5' of the MCneo insertion in exon 3 and a primer derived from exon 4. The PCK products are derived from ~4,000 splenic cell equivalents and are compared with PCR products obtained from 200, 2,000, or 20,000 molecules of control IL-7R. cDNA. Reagent only (0) and genomic DNA controls are included and the positions of various HindlII X size markers are shown.

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